Novel Assay Analyzing Tropism between Adipose-Derived Stem Cells and Breast Cancer Cells Reveals a Low Oncogenic Response

Abstract

Introduction: In the surgical world of breast cancer reconstruction, fat grafting is commonly viewed as an oncogenic risk. Scientific studies add confusion, given the stark lack of clinical evidence suggesting pro-oncogenic links. Typically, classic migration assays (e.g., Boyden chamber) between adipose-derived stem cells and breast cancer cells define this cell relationship as pro-oncogenic. Objective: We sought to develop a new migration model which better explains existing clinical data. Methods: Silicon chambers were used to seed isolated populations of cells simultaneously in culture dish. Once cells had adhered, chambers were removed and cells were allowed to follow natural trophic cues. Multiple permutations of MDA-MB-231, MCF-7, HS-27, and ASCs were engineered. Cells were stained with MitoTracker for fluorescent visualization. A human cytokine array (RayBiotech) was performed on the media of migrating assays. Cellular tropism and blot intensity were quantitatively measured in Image J. Results: An in vitromodel was successfully constructed where ASCs reproducibly and freely migrated. Cytokine arrays reveal higher levels of IL-6 and CCL2 in the media of Boyden chambers containing ASCs and MDA-MB-231, compared to the novel assay, comprised of the same cell numbers, types, and incubation times. Conclusion: These data collectively show for the first time the attraction of ASCs to malignant breast cancer cells; a phenomenon which many ASC studies infer. The cytokine profile of the novel system described is less oncogenic than the commonly described Boyden chamber. These data integrate better into the clinical data, which fail to link cancer recurrence with fat grafting.

Breast fat grafting and cancer: a systematic review of the science behind enhancements and concerns

“…BT-474 co-culture also increased proliferation, with TNF-alpha upregulation ( 9 ). Natural tropism of ADSCs towards breast cancer cells has been evaluated after independent cultures were done in silicon chambers, then chambers were removed and ADSCs tropism was confirmed, thus indicating attraction of ADSCs to malignant breast cells ( 10 ).…”

The paracrine effects of adipocytes on lipid metabolism in doxorubicin-treated triple negative breast cancer cells

“…The experimental treatment protocol included four experimental treatment groups: (i) control, (ii) adipocyte-conditioned media (CM), (iii) doxorubicin (Dox), and (iv) a combination of adipocyte-conditioned media and doxorubicin (Dox+CM) ( Table 1 ). The adipocyte-conditioned media treatment groups consisted of 30% adipocyte-conditioned media and 70% growth media ratio [ 46 , 47 ], to maintain cellular-viability and to still elicit the desired response.…”

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“…The exosomes, released from the adipocyte s and ASCs, are emerging as a new type in the crosstalk between breast tumors and adipocytes ( Sauter et al, 2019 ; Teufelsbauer et al, 2019 ). Previously, Lin et al (2013) investigated the effect of ASC-exos on breast cancer MCF7 cells, showing that ASC-exos activated the Wnt and Hh signaling pathways to strengthen tumor cell migration.…”